Phorbol diester binding sites appear very stable biologically showing no significant variaion in number, affinity for 3H-PDBu or down modulation among preneoplastic cells deliberately selected for resistance to TPA induced mitogenesis or promotion. Nor does malignant transformaion detectably perturb these binding sites in mouse or human cells. Loss of EGF receptors correlates with loss of the mitogenic response to TPA in monolayer culture but has no effects on 3H-PDBu binding parameters or promotion of transformation. Transforming growth factor (TGF) from a human tumor line can promote anchorage independence in a TPA promotable mouse epidermal cell line lacking EGF receptors and responsiveness to EGF. Current studies seek to identify cell surface receptors for TGF distinct from EGF receptors on this cell line as well as inducibility of TGF secretion by tumor promoters.